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Donors FMO3 polymorphisms affect tacrolimus elimination in Chinese liver transplant patients

Lei Ren1, Mujian Teng1, Tao Zhang2

  • 1Department of Hepatobiliary Pancreatic Surgery, Shandong Qianfoshan Hospital, Shandong University, Jinan 250014, China.

Pharmacogenomics
|January 14, 2017
PubMed
Abstract

Insights

Donor FMO3 gene variants (rs1800822 and rs909530) significantly influence tacrolimus drug metabolism in liver transplant recipients. These genetic factors predict faster tacrolimus elimination, impacting patient treatment.

Area of Science:

  • Pharmacogenomics
  • Transplant Medicine
  • Drug Metabolism

Background:

  • Tacrolimus is a crucial immunosuppressant after liver transplantation.
  • Flavin-containing monooxygenase (FMO) enzymes, particularly FMO3, are implicated in drug metabolism.
  • The role of FMO3 genetic variations in tacrolimus pharmacokinetics post-liver transplant remains under-investigated in Chinese populations.

Purpose of the Study:

  • To investigate the association between FMO3 single nucleotide polymorphisms (SNPs) and tacrolimus elimination in Chinese liver transplant patients.
  • To explore the combined impact of FMO3 and CYP3A5 genotypes on tacrolimus pharmacokinetics.

Main Methods:

  • Genotyping of FMO3 SNPs (rs1800822, rs909530) and CYP3A5 rs776746 in 110 Chinese liver transplant recipients.
  • Analysis of tacrolimus concentration-to-dose ratios and correlation with genetic polymorphisms.

Main Results:

  • Donor FMO3 rs1800822 allele T and rs909530 allele T were associated with faster tacrolimus elimination.
  • Combined FMO3 polymorphisms (rs1800822 and rs909530) significantly impacted tacrolimus elimination (p = 0.0221).
  • The number of T alleles for donor FMO3 rs1800822 and rs909530 independently predicted tacrolimus concentration-to-dose ratios at weeks 2, 3, and 4.

Conclusions:

  • Donor FMO3 polymorphisms play a role in modulating tacrolimus elimination after liver transplantation.
  • Genetic screening of FMO3 variants may aid in personalized tacrolimus dosing strategies.
  • Further research is warranted to elucidate the precise mechanisms of FMO3 in tacrolimus metabolism.
Keywords:
CYP-450 3A5FMO3pharmacogenomicstacrolimus

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